Does Age at Menarche Differ Between Patients With Multiple Sclerosis and Healthy Controls?: An Updated Systematic Review and Meta-Analysis Publisher



Shahraki Z¹ ; Rastkar M^{2, 3} ; Rastkar E⁴ ; Ghajarzadeh M³ ; Mohammadifar M³ Show Affiliations
Source: Journal of Family and Reproductive Health Published:2025

Abstract

Objective: Sex hormones play role in development of autoimmune diseases such as multiple sclerosis (MS). In our previous systematic review, we included three studies and reported the pooled odds ratio (OR) for increasing 1 year of age at menarche and risk of MS as 0.88. So, we designed this systematic review and meta-analysis to estimate the pooled mean age at menarche difference between women with MS and controls and also update the odds of developing MS by increasing age at menarche. Materials and methods: We performed a comprehensive systematic search on PubMed, Scopus, EMBASE, and Web of Science on July 1st, 2023. Also, grey literature including conference abstracts and references of the references were investigated to find potentially relevant articles. Results: A total 634 records were retrieved by systematic search. Also, one relevant record was identified from grey literature. After deduplication, 331 articles were remained for title/abstract screening and of those, 29 full-texts were evaluated. Finally, 15 studies were included in final analysis. The SMDs of age at menarche (control group – case group) ranged between-0.18 and 1.41. The pooled SMD of age at menarche (controls-cases) was 0.17 (95% CI: 0.09-0.25) (I2=85.1%, p<0.001). OR for age at menarche and risk of MS ranged between 0.8 and 1.76, and the pooled OR for increasing 1 year of age at menarche estimated as 0.92(95% CI: 0.89-0.94) (I2=41.6%, P=0.07). Conclusion: The results of this systematic review show that the mean age at menarche is higher in controls than women with MS, and the risk of MS decreases by increasing age at menarche. © 2025 Tehran University of Medical Sciences.